This Program Project Grant Application (PPG) is a revised version of a Proposal which we initially submitted in response to RFA HL-00-008 to seek funding for a Program of Excellence in Gene Therapy (PEGT) at St. Elizabeth's Medical Center (SEMC)/Tufts University School of Medicine (TUSM) with collaboration from the Cleveland Clinic Department of Surgery, and the Biostatistics Center, George Washington University, Rockville, Maryland. The PPG consists of three Clinical Projects and two Pre-clinical Projects, supported by four Cores. Dr. Jeffrey M. Isner, Principal Investigator (PI) with overall responsibility for the PPG, will serve as Project Director for (clinical) Project 1, "VEGF Gene Transfer for Diabetic Neuropathy." Dr. Douglas Losordo will direct (clinical) Project 2, "VEGF Gene Transfer to Prevent Coronary Artery Restenosis." (Clinical) Project 3, "VEGF Gene Transfer to Promote Angiogenesis in Patients with Advance Heart Failure," will be directed by Dr. Patrick McCarthy, Surgical Director of the Cleveland Clinic Kaufman Center for Heart Failure. Ken Walsh, Ph.D. will serve as Project Director for (pre-clinical) Project 4, " Molecular Studies of Heart Failure." Dr. Takayuki Asahara will direct (pre-clinical) Project 5, "Endothelial Progenitor Cell Gene Transfer." The research productivity and functional capacity of the PPG will be enhanced by four Cores. Core A, the Plasmid Core, will provide clinical grade plasmid DNA vector, and will be supervised by Dr. Walsh. Core B, the Administrative Core, directed by Dr. Losordo, will supply critical administrative assistance. Drs. Losordo and Walsh will also direct Core C, the Training Core. Core D, the Data Management Core, directed by Kathryn Hirst, Ph.D. Research Associate Professor of the Biostatistics Center, George Washington University will assist with data management and analysis, and will also ensure compliance with all appropriate regulatory bodies. The studies and organization outlined in this PPG are intended to provide high quality and credible clinical as well as pre-clinical research studies of gene transfer that will represent meaningful contributions to both the scientific community and lay public.